Aβ stimulates microglial activation through antizyme-dependent downregulation of ornithine decarboxylase

doi:10.1002/jcp.27659

中山醫學大學機構典藏 CSMUIR > 醫學院 > 生化微生物免疫研究所 > 期刊論文 > Item 310902500/19902

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/19902

Title:	Aβ stimulates microglial activation through antizyme-dependent downregulation of ornithine decarboxylase
Authors:	Li, H.-H. Liu, G.-Y. Lin, C.-L.
Date:	2019-03
Issue Date:	2019-03-12T03:40:25Z (UTC)
ISSN:	00219541
Abstract:	Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders. Its pathology is associated with the deposition of amyloid β (Aβ), an abnormal extracellular peptide. Moreover, its pathological progression is closely accompanied by neuroinflammation. Specifically, Aβ-associated microglial overactivation may have the central role in AD pathogenesis. Interestingly, arginine metabolism may contribute to the equilibrium between M1 and M2 microglia. However, little is known about the involvement of arginine metabolism in Aβ-induced microglial neuroinflammation and neurotoxicity. Moreover, the underlying mechanism by which Aβ induces the transition of microglia to the M1 phenotype remains unclear. In this study, we investigated the role of Aβ in mediating microglial activation and polarization both in vitro and in vivo. Our results demonstrated that under the Aβ treatment, ornithine decarboxylase (ODC), a rate-limiting enzyme in the regulation of arginine catabolism, regulates microglial activation by altering the antizyme (AZ) + 1 ribosomal frameshift. Furthermore, the restoration of ODC protein expression levels has profound effects on inhibition of Aβ-induced M1 markers and thus attenuates microglial-mediated cytotoxicity. Altogether, our findings suggested that Aβ may contribute to M1-like activation by disrupting the balance between ODC and AZ in microglia. © 2018 Wiley Periodicals, Inc.
URI:	https://ir.csmu.edu.tw:8080/ir/handle/310902500/19902
Relation:	Journal of Cellular Physiology Volume 234, Issue 6, June 2019, Pages 9733-9745
Appears in Collections:	[生化微生物免疫研究所] 期刊論文

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